Selective serotonin reuptake inhibitors are used in the treatment of psychiatric disorders but are associated with high incidence of sexual dysfunction such as ejaculation disorders by sertraline and fluoxetine, erection disorders by paroxetine. The aim of this study is to evaluate the effects of paroxetine, sertraline and fluoxetine on relaxation of smooth muscle of corpus cavernosum on the basis of nitric oxide (NO). Male mice were killed by cervical dislocation and their penile tissues were immediately removed. The tissues were incubated in organ baths containing Krebs solution at 37 degrees C and bubbled with 95% O-2 and 5% CO2. The corpus cavernosum strips were contracted with 10-5 m phenylephrine (PHE) and relaxed with either paroxetine, sertraline, fluoxetine (10-8-10-4 m) or electrical field stimulation (EFS). The effects of paroxetine, sertraline and fluoxetine were examined on EFS-induced relaxations. While paroxetine did not show any effect on the corpus cavernosum strips precontracted with PHE, sertraline and fluoxetine caused a relaxation at concentrations of 3 x 10-5-10-4 m. The relaxations induced by sertraline and fluoxetine were completely abolished by l-NAME, but not d-NAME. The relaxations induced by EFS could be inhibited by l-NAME but not d-NAME. Paroxetine inhibited the relaxations at high concentrations. l-Arginine potentiated the relaxations induced by EFS; however in the presence of paroxetine these relaxations were not observed. In contrast, sertraline (10-8-10-5 m) and fluoxetine (10-8-10-5m) increased the relaxations induced by EFS. Sertraline and fluoxetine seem to be releasing some relaxing factor(s) and this factor may be NO. Paroxetine probably has a NOS inhibitory activity either on nNOS or eNOS, in contrast to sertraline and fluoxetine.